The proposal outlines studies directed at clinical, biochemical and genetic aspects of hypertriglyceridemia. It focuses on the pathogenesis and inheritance of massive hypertriglyceridemia and on the role of lipoprotein lipase in the metabolism of triglyceride-rich lipoproteins in man. The project is designed to to test the hypothesis that partial lipoprotein lipase deficiency exists in selected pedigrees and contributes to the pathogenesis of acquired hyperlipoproteinemia. Kindred of propositi selected for massive lipemia will be studied in detail. Postheparin lipoprotein lipase activity will be measured prior to and following estrogen provocative challenge. The in vitro assay, based on selective immunochemical precipitation of hepatic triglyceride hydrolase activity will be reexamined for specificity and reproducibility. An alternative rapid and sensitive assay, based on potentiometric (titrimetric pH stat) methodology will be developed with emphasis on specificity. Toward this end, studies of substrate specificity, reaction kinetics and activator requirements will be initiated on purified milk lipoprotein lipase and human postheparin plasma lipoprotein lipase. Finally, clinical and biochemical studies will be undertaken to determine whether there are abnormalities in either the substrate or the activating apolipoprotein peptides in hypertriglyceridemic individuals. Data will be analyzed to determine whether clearly defined subpopulations exist among first-degree relatives at risk for hypertriglyceridemia and partial lipoprotein lipase deficiency. Segregation analysis of simple Mendelian inheritance will be performed if distinct subpopulations are identified. These studies will be undertaken in selected families since one may assume that the data are obtained from groups of individuals with discrete biochemical defect(s). Data generated by the investigations will clarify the clinical, genetic and biochemical attributes of a subset of individuals potentially at risk for coronary heart disease.